Empowering informed choices

“NIPT is incredible. It offers you so much information with such little risk. To have that peace of mind really made a difference for us.”

– Talia and Dan

Noninvasive Prenatal Testing (NIPT)

Advancing Breakthroughs with Genomic Solutions in NIPT

Evolving noninvasive screening options, such as noninvasive prenatal tests (NIPT), offer early genetic screening for chromosomal conditions using just one tube of blood—as early as 10 weeks into a patient’s pregnancy.

Other types of prenatal screening and diagnostic tests may require more than one office visit, multiple blood draws, or carry a higher risk of false positive results. Diagnostic tests, such as chorionic villus sampling (CVS) or amniocentesis, provide definite results for most chromosome conditions but have an associated risk of miscarriage.

NIPT poses minimal risk to the mother or baby with high detection rates and low false positives. The American Congress of Obstetricians and Gynecologists (ACOG) and International Society of Prenatal Diagnosis (ISPD), along with other professional societies, have stated that NIPT is an available screening option for all pregnant women.1,2

The verifi Prenatal Test is one such noninvasive test that screens for aneuploidy of chromosomes 21, 18, and 13. Additional screening is available for sex chromosome aneuploidies and select microdeletions in singleton pregnancies. In twin pregnancies, screening for aneuploidy in chromosomes 21, 18, and 13 and the option to screen for the absence of the Y chromosome is available. The results are reported in approximately 3–5 days after the sample is received. Depending on demand, the time to report may vary.

Publication: 85,000 NIPT Cases

Noninvasive prenatal testing in the general obstetric population: Clinical performance and counseling considerations in over 85,000 cases.

Click on the below to view the sensitivity and specificity data table.

Sensitivity and Specificity for Trisomies 21, 18, and 13

Condition

Sensitivity

95% CI

Specificity

95% CI

Trisomy 21

99.2%

98.5-99.6%

99.91%

99.86–99.95%

Trisomy 18

96.3%

94.3–97.9%

99.87%

99.80–99.93%

Trisomy 13

91.0%

85.0–95.6%

99.87%

99.74–99.95%

NIPT performance for trisomies 21, 18, and 13 in singleton pregnancies as reported in a large, independent meta-analysis3

Data from a meta-analysis of 37 published NIPT studies between January, 2011 and January, 2015. Sensitivity and specificity are test specific, not patient specific. As such, they are not expected to change significantly based on an individual patient’s clinical picture (eg. maternal age, ultrasound findings).

Performance Metrics Considerations After Screening

Positive Predictive Value (PPV)

A test’s PPV can help you determine how likely a positive result is to be a true positive. PPV is based on the sensitivity and specificity of the test AND the prevalence of the condition in the population being tested.

NIPT PPVs by maternal age

PPVs calculated using sensitivity and specificity data from a meta-analysis of 37 NIPT studies3 and published estimates of aneuploidy prevalence at 10 weeks gestation for different maternal age groups.4-6 The potential PPV range, illustrated by the error bars, was calculated using 95% confidence intervals (CI) for sensitivity and specificity.

Why Prevalence Matters for PPVs

Because the prevalence of autosomal trisomies (eg, trisomy 21) increases with maternal age, so do the PPVs. Trisomy 21 is the most prevalent autosomal trisomy in livebirths. Thus, the PPVs are higher for trisomy 21 than for trisomies 18 and 13, which are less common. The PPVs above are calculated based on age-related prevalence; the presence of other aneuploidy risk factors (e.g. ultrasound abnormalities) would likely increase the PPVs over those shown here.

Trisomy 21 PPVs

PPVs calculated using sensitivity and specificity data from a meta-analysis of 37 NIPT studies3 and a large study of first trimester combined screening8 and published estimates of trisomy 21, trisomy 18, and trisomy 13 prevalence at 10 weeks’ gestation for different maternal ages.4 The potential PPV ranges for each test, illustrated by error bars, were calculated using 95% confidence intervals (CI) for sensitivity and specificity.

Why Specificity Matters for PPVs

While PPVs are lower in younger women, PPVs for NIPT will be higher than those of traditional serum screening at all maternal ages because NIPT has significantly higher specificity (a lower false positive rate).5

For patients with a positive NIPT result:

Counsel the patient about the NIPT results, the likelihood of a true positive (PPV), and the recommendation for confirmatory diagnostic testing.9,10

To calculate a patient’s individual PPV, you may wish to use the PPV calculator endorsed by ACOG.11

Assessing Test Failure Rate

The verifi Prenatal Test has the lowest failure rate in the industry of 0.1%, excluding administered failed samples—that means that 99.9% of the time a result is provided12. It uses next-generation sequencing to analyze cfDNA fragments across the whole genome, which has proven advantages over other NIPT methodologies such as targeted sequencing and array-based methods. Test failure rates are substantially lower with whole-genome sequencing versus other methodologies.12-15

That’s important, and clinically relevant, because not only do test failures negatively impact patient care, they also adversely affect test metric parameters such as sensitivity, specificity, and PPV. By choosing the verifi Prenatal Test, the clinical impact of failures can be reduced.12

The Illumina Difference

We’re committed to providing laboratories and health care partners with comprehensive solutions and test options to improve human health. Published data shows, that NGS with whole-genome sequencing (WGS) is the NIPT technology of choice—when compared to targeted approaches.

With over 99.7% of NIPT samples in these studies run on Illumina NGS technology, we’re helping advance breakthrough in prenatal screening. It’s what makes the verifi Prenatal Test, with the lowest failure rate of any noninvasive prenatal test on the market, the best choice for patients.

Click on the below to view the samples run data table.

99.7% of NIPT Samples in Published Studies Run on Illumina NGS Systems (2011-2015)

Test (Company)

Current technology platform

Platform provider

Number of published samples

Illumina NGS

Ion Proton NGS

Affymetrix array

Bambni Test (Berry Genomics)

NGS

Illumina

3,268

0

0

MaterniT21 PLUS Test (Sequenom)

NGS

Illumina

293,243

0

0

NIFTY Test (BGI)

NGS

Illumina

168,655

0

0

Panorama Prenatal Screen (Natera)

NGS

Illumina

55,077

0

0

PrenaTest (LifeCodexx AG)

NGS

Illumina

504

0

0

verifi Prenatal Test (Illumina)

NGS

Illumina

113,561

0

0

IONA Test (Premaltha)

NGS

Ion Proton

0

684

0

Harmony Prenatal Test (Arlosa)*

Array

Affymetrix

44,313

0

1,677

Total

678,621

684

1,677

A PubMed search for "cell-free, DNA, prenatal," "noninvasive prenatal testing," and "noninvasive prenatal screening" was performed on November 30, 2015. All validation and clinical studies using unique samples were included, where a current clinical NIPT provider performed sample analysis. Case studies and studies published in a language other than English were excluded. A total of 59 published studies were surveyed. Data calculations on file. Illumina, Inc. 2015. NGS = next-generation sequencing; either whole-genome or targeted.

*In 2014, Ariosa switched from sequencing to arrays for clinical samples despite limited published data on this platform.

Test Failures May Lead to Invasive Procedures.†

Theoretical example of the number of invasive procedures requested due to NIPT failure and false positive rates of the assays. Failure rates include assay failures and samples rejected due to low fetal fraction. Assay failure rate for the Harmony test is based on NGS studies and may not be consistent with actual test results achieved using the array-based Harmony Test currently in use.12-18

†Affected pregnancies with a screening test failure were excluded from the number of detected T21.

Getting Started with the verifi Prenatal Test

Learn more about our noninvasive prenatal testing solution by selecting an option below.

References

Benn P, Borrell A, Chiu RWK, et al. Position statement from the Chromosome Abnormality Screening Committee on behalf of the Board of the International Society for Prenatal Diagnosis. Prenat Diagn. 2015;35(8):725-734.

The verifi Prenatal Test was developed by, and its performance characteristics were determined by Verinata Health, Inc. a wholly owned subsidiary of Illumina, Inc. The VHI laboratory is CAP-accredited and certified under the Clinical Laboratory Improvement Amendments (CLIA) as qualified to perform high complexity clinical laboratory testing. It has not been cleared or approved by the U.S. Food and Drug Administration.